Actions of the Japanese pancreas and islet transplantation association regarding transplanted human islets isolated using liberase HI

T. Saito, T. Anazawa, M. Gotoh, S. Uemoto, Takashi Kenmochi, Y. Kuroda, S. Satomi, T. Itoh, Y. Yasunami, T. Kitamoto, S. Mohri, S. Teraoka

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Abstract

Purpose The potential for introducing transmissible spongiform encephalopathy (TSE) into islet cells was indicated by recognizing that Liberase HI is isolated from Clostridium histolyticum grown in media containing brainheart infusion broth. A national team within the Japanese Pancreas and Islet Transplantation Association implemented an islet transplantation program in Japan using Liberase HI. The program comprised 65 islet isolations from nonheart-beating donors and 34 transplants into 18 patients. Herein, we have summarized how the Association followed these recipients over the long term. Procedures We established an ad hoc committee to follow recipients transplanted with islets isolated using Liberase HI after becoming informed of the associated dangers of using this enzyme. We also stopped islet transplantations using Liberase. The committee addressed the major concerns of the risk of the collagenase being contaminated with TSE and of the recipient follow-up. All recipients were examined by diffusion MRI and EEG and then scheduled for evaluation and follow-up by specialists in Creutzfeldt-Jakob disease (CJD). Bioassays of bovine spongiform encephalopathy prions in the enzyme proceeded using knock-in mice expressing bovine prion protein. These assays could detect contaminating prions at a dilution of 1 × 10 4. After inactivating its collagenase activity, Liberase HI was injected into the abdominal cavities of knock-in mice. Four months later, prion infectivity in Liberase HI was evaluated by immunohistochemical staining and Western blotting of spleen homogenates using anti-prion protein antibodies. Main findings Western blotting and immunohistochemical staining did not detect prions in Liberase HI. Diffusion MRI and EEG evaluations performed by CJD specialists confirmed that none of the transplanted recipients had CJD. Conclusions Three years of follow-up revealed that none of the Japanese recipients of islet transplants developed CJD. Prion bioassays showed that the Liberase HI used to isolate islets for transplantation was free of infectious TSE prions.

Original languageEnglish
Pages (from-to)4213-4216
Number of pages4
JournalTransplantation Proceedings
Volume42
Issue number10
DOIs
Publication statusPublished - 01-12-2010

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Pancreas Transplantation
Islets of Langerhans Transplantation
Prions
Creutzfeldt-Jakob Syndrome
Prion Diseases
Diffusion Magnetic Resonance Imaging
Collagenases
Biological Assay
Clostridium histolyticum
Electroencephalography
Western Blotting
Staining and Labeling
Bovine Spongiform Encephalopathy
Liberase
Abdominal Cavity
Enzymes
Islets of Langerhans
Japan
Spleen
Tissue Donors

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

Saito, T. ; Anazawa, T. ; Gotoh, M. ; Uemoto, S. ; Kenmochi, Takashi ; Kuroda, Y. ; Satomi, S. ; Itoh, T. ; Yasunami, Y. ; Kitamoto, T. ; Mohri, S. ; Teraoka, S. / Actions of the Japanese pancreas and islet transplantation association regarding transplanted human islets isolated using liberase HI. In: Transplantation Proceedings. 2010 ; Vol. 42, No. 10. pp. 4213-4216.
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abstract = "Purpose The potential for introducing transmissible spongiform encephalopathy (TSE) into islet cells was indicated by recognizing that Liberase HI is isolated from Clostridium histolyticum grown in media containing brainheart infusion broth. A national team within the Japanese Pancreas and Islet Transplantation Association implemented an islet transplantation program in Japan using Liberase HI. The program comprised 65 islet isolations from nonheart-beating donors and 34 transplants into 18 patients. Herein, we have summarized how the Association followed these recipients over the long term. Procedures We established an ad hoc committee to follow recipients transplanted with islets isolated using Liberase HI after becoming informed of the associated dangers of using this enzyme. We also stopped islet transplantations using Liberase. The committee addressed the major concerns of the risk of the collagenase being contaminated with TSE and of the recipient follow-up. All recipients were examined by diffusion MRI and EEG and then scheduled for evaluation and follow-up by specialists in Creutzfeldt-Jakob disease (CJD). Bioassays of bovine spongiform encephalopathy prions in the enzyme proceeded using knock-in mice expressing bovine prion protein. These assays could detect contaminating prions at a dilution of 1 × 10 4. After inactivating its collagenase activity, Liberase HI was injected into the abdominal cavities of knock-in mice. Four months later, prion infectivity in Liberase HI was evaluated by immunohistochemical staining and Western blotting of spleen homogenates using anti-prion protein antibodies. Main findings Western blotting and immunohistochemical staining did not detect prions in Liberase HI. Diffusion MRI and EEG evaluations performed by CJD specialists confirmed that none of the transplanted recipients had CJD. Conclusions Three years of follow-up revealed that none of the Japanese recipients of islet transplants developed CJD. Prion bioassays showed that the Liberase HI used to isolate islets for transplantation was free of infectious TSE prions.",
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Saito, T, Anazawa, T, Gotoh, M, Uemoto, S, Kenmochi, T, Kuroda, Y, Satomi, S, Itoh, T, Yasunami, Y, Kitamoto, T, Mohri, S & Teraoka, S 2010, 'Actions of the Japanese pancreas and islet transplantation association regarding transplanted human islets isolated using liberase HI', Transplantation Proceedings, vol. 42, no. 10, pp. 4213-4216. https://doi.org/10.1016/j.transproceed.2010.09.142

Actions of the Japanese pancreas and islet transplantation association regarding transplanted human islets isolated using liberase HI. / Saito, T.; Anazawa, T.; Gotoh, M.; Uemoto, S.; Kenmochi, Takashi; Kuroda, Y.; Satomi, S.; Itoh, T.; Yasunami, Y.; Kitamoto, T.; Mohri, S.; Teraoka, S.

In: Transplantation Proceedings, Vol. 42, No. 10, 01.12.2010, p. 4213-4216.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Actions of the Japanese pancreas and islet transplantation association regarding transplanted human islets isolated using liberase HI

AU - Saito, T.

AU - Anazawa, T.

AU - Gotoh, M.

AU - Uemoto, S.

AU - Kenmochi, Takashi

AU - Kuroda, Y.

AU - Satomi, S.

AU - Itoh, T.

AU - Yasunami, Y.

AU - Kitamoto, T.

AU - Mohri, S.

AU - Teraoka, S.

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Purpose The potential for introducing transmissible spongiform encephalopathy (TSE) into islet cells was indicated by recognizing that Liberase HI is isolated from Clostridium histolyticum grown in media containing brainheart infusion broth. A national team within the Japanese Pancreas and Islet Transplantation Association implemented an islet transplantation program in Japan using Liberase HI. The program comprised 65 islet isolations from nonheart-beating donors and 34 transplants into 18 patients. Herein, we have summarized how the Association followed these recipients over the long term. Procedures We established an ad hoc committee to follow recipients transplanted with islets isolated using Liberase HI after becoming informed of the associated dangers of using this enzyme. We also stopped islet transplantations using Liberase. The committee addressed the major concerns of the risk of the collagenase being contaminated with TSE and of the recipient follow-up. All recipients were examined by diffusion MRI and EEG and then scheduled for evaluation and follow-up by specialists in Creutzfeldt-Jakob disease (CJD). Bioassays of bovine spongiform encephalopathy prions in the enzyme proceeded using knock-in mice expressing bovine prion protein. These assays could detect contaminating prions at a dilution of 1 × 10 4. After inactivating its collagenase activity, Liberase HI was injected into the abdominal cavities of knock-in mice. Four months later, prion infectivity in Liberase HI was evaluated by immunohistochemical staining and Western blotting of spleen homogenates using anti-prion protein antibodies. Main findings Western blotting and immunohistochemical staining did not detect prions in Liberase HI. Diffusion MRI and EEG evaluations performed by CJD specialists confirmed that none of the transplanted recipients had CJD. Conclusions Three years of follow-up revealed that none of the Japanese recipients of islet transplants developed CJD. Prion bioassays showed that the Liberase HI used to isolate islets for transplantation was free of infectious TSE prions.

AB - Purpose The potential for introducing transmissible spongiform encephalopathy (TSE) into islet cells was indicated by recognizing that Liberase HI is isolated from Clostridium histolyticum grown in media containing brainheart infusion broth. A national team within the Japanese Pancreas and Islet Transplantation Association implemented an islet transplantation program in Japan using Liberase HI. The program comprised 65 islet isolations from nonheart-beating donors and 34 transplants into 18 patients. Herein, we have summarized how the Association followed these recipients over the long term. Procedures We established an ad hoc committee to follow recipients transplanted with islets isolated using Liberase HI after becoming informed of the associated dangers of using this enzyme. We also stopped islet transplantations using Liberase. The committee addressed the major concerns of the risk of the collagenase being contaminated with TSE and of the recipient follow-up. All recipients were examined by diffusion MRI and EEG and then scheduled for evaluation and follow-up by specialists in Creutzfeldt-Jakob disease (CJD). Bioassays of bovine spongiform encephalopathy prions in the enzyme proceeded using knock-in mice expressing bovine prion protein. These assays could detect contaminating prions at a dilution of 1 × 10 4. After inactivating its collagenase activity, Liberase HI was injected into the abdominal cavities of knock-in mice. Four months later, prion infectivity in Liberase HI was evaluated by immunohistochemical staining and Western blotting of spleen homogenates using anti-prion protein antibodies. Main findings Western blotting and immunohistochemical staining did not detect prions in Liberase HI. Diffusion MRI and EEG evaluations performed by CJD specialists confirmed that none of the transplanted recipients had CJD. Conclusions Three years of follow-up revealed that none of the Japanese recipients of islet transplants developed CJD. Prion bioassays showed that the Liberase HI used to isolate islets for transplantation was free of infectious TSE prions.

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